Obesity: BMI ≥ 30 kg/m2 or greater

Obesity is due in part to an energy imbalance

Calorie consumption exceeds calorie expenditure

Who is a candidate for pharmacological intervention for obesity?◦ BMI > 30

◦ BMI > 27 with at least two comorbidities (e.g. diabetes, hypertension)

The majority of drugs approved to treat obesity have short-term indications

Anorexiants◦ Diethylpropion

◦ Phentermine

Lipase inhibitor◦ Orlistat

Serotonin agonist◦ Lorcaserin

Combination products◦ Phentermine/Topiramate

Phentermine

Diethylpropion

Mechanism of action: ◦ Phentermine increases the release of norepinephrine

and dopamine and by inhibiting their reuptake

◦ Diethylpropion has similar effects on norepinephrine

Tolerance to the weight loss effect develops within weeks, and weight loss plateaus

Discontinuation is usually recommended once

plateau is reached

Phentermine and diethylpropion are primarlyexcreted via kidneys

Diethylpropion undergoes extensive first-pass metabolism, many of the metabolites are active

Adverse effects: ◦ All anorexiants are classified as controlled substances due

to the potential for dependence or abuse

◦ Dry mouth, headache, insomnia, and constipation

◦ Heart rate and blood pressure may be increased

Should be avoided in uncontrolled hypertension, cardiovascular disease, arrhythmias, heart failure, or stroke

Concomitant use of anorexiants with MAOIs or other sympathomimetics should be avoided

Lipase inhibitor

Use is limited by GI adverse effects

Mechanism of action: ◦ Orlistat inhibits gastric and pancreatic lipases, decreasing the

breakdown of dietary fat into smaller molecules ◦ Orlistat decreases fat absorption by about 30%◦ The loss of calories from decreased absorption of fat is the main

cause of weight loss

Administered orally with each meal that contains fat

It has minimal systemic absorption and is mainly excreted in the feces

No dosage adjustments are required in patients with renal or hepatic dysfunction

Adverse effects: Gastrointestinal symptoms, such as oily spotting,

flatulence with discharge, fecal urgency, and increased defecation◦ These effects may be minimized through a low-fat diet

and the use of cholestyramine

Pancreatitis and liver injury (Rare) Contraindicated in pregnancy and in patients with

chronic malabsorption syndrome or cholestasis Interferes with the absorption of fat-soluble

vitamins and β-carotene

Lorcaserin

Used for chronic weight management

Mechanism of action: ◦ Lorcaserin selectively activates 5-HT2C receptors, in

the CNS

◦ This stimulates pro-opiomelanocortin neurons, which activate melanocortin receptors, causing a decrease in appetite

Adverse effects:

Nausea, headache, dry mouth, dizziness, constipation, and lethargy

Mood changes, suicidal ideation can occur (Rare)

Valvulopathy has been reported

The combination of phentermine and topiramatehas been approved for long-term use in the treatment of obesity

Because of the sedating effects of topiramate, the stimulant phentermine was added

The dose is excalated every 2 weeks

If a patient does not achieve a 5% weight loss after 12 weeks on the highest dose, it should be discontinued

Should not be stopped abruptly as seizures may be precipitated

Topiramate has been associated with birth defects including cleft palate

Adverse effects ◦ Paresthesias, suicidal ideation, and cognitive dysfunction

◦ Increased heart rate

Topiramate may reduce efficacy of oral contraceptives